Cerebroprotective effects of flunarizine in an experimental rat model of cardiac arrest.
A rat cardiopulmonary arrest model was used to study the effects of flunarizine on survival and on the development of postischemic brain damage. Ischemia was induced by a combination of hypovolemia and intracardiac injection of a cold potassiumchloride solution. To validate the model; survival rate and histological damage were assessed after ischemic periods ranging from 5 to 20 minutes. A 6-minute cardiac arrest period was withheld for further therapeutic investigations. In one group (n = 12), flunarizine was administered successively in doses of 0.5 mg/kg intravenous at 5 minutes, 10 mg/kg intraperitoneal at 1 hour, and 20 mg/kg orally at 16 and 24 hours after recirculation. The second group (n = 13) received only the vehicle. Flunarizine, although not affecting mortality; significantly reduced the mean number of ischemic neurons in CA1 hippocampus from 83% in the control to 44% in the drug-treated series (P = 0.014). The results are indicative of the usefulness of this cardiac arrest model to study morphologic aspects of cerebral injury. The results obtained with flunarizine show the effectiveness of this drug even when it is administered after a severe ischemic insult such as global complete ischemia.
Lu
H R
HR
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing.
Van Reempts
J
J
Haseldonckx
M
M
Borgers
M
M
Janssen
P A
PA
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005444:Flunarizine / Q000627:therapeutic use*; D006323:Heart Arrest / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012151:Resuscitation; D012769:Shock / Q000473:pathology; D013997:Time Factors
D005444:Flunarizine